N. Sowada, M.O. Hashem, R. Yilmaz, M. Hamad, N. Kakar, H Thiele, S.T Arold, H. Bode, F.S Alkuraya, G. Borck
Human Genetics, volume 136, issue 11-12, pp. 1455-1461, (2017)
Developmental and epileptic encephalopathies (DEE) are a heterogeneous
group of neurodevelopmental disorders with poor prognosis. Recent
discoveries have greatly expanded the repertoire of genes that are
mutated in epileptic encephalopathies and DEE, often in a de novo
fashion, but in many patients, the disease remains molecularly
uncharacterized. Here, we describe a new form of DEE in patients with
likely deleterious biallelic variants in PTPN23.
The phenotype is characterized by early onset drug-resistant epilepsy,
severe and global developmental delay, microcephaly, and sometimes
premature death. PTPN23 encodes a
tyrosine phosphatase with strong brain expression, and its knockout in
mouse is embryonically lethal. Structural modeling supports a
deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.